19.6 Substituents and Acid Strength

1
19.6Substituents and Acid Strength
2
Substituent Effects on Acidity
standard of comparison is acetic acid (X H)
Ka 1.8 x 10-5pKa 4.7
3
Substituent Effects on Acidity

• alkyl substituents have negligible effect

4
Substituent Effects on Acidity

• electronegative substituents increase acidity

5
Substituent Effects on Acidity

• electronegative substituents withdraw electrons
  from carboxyl group increase K for loss of H

6
Substituent Effects on Acidity
X
Ka
pKa

H
1.8 x 10-5
4.7
1.4 x 10-3
2.9
Cl
ClCH2
1.0 x 10-4
4.0
ClCH2CH2
3.0 x 10-5
4.5

• effect of electronegative substituent decreases
  as number of bonds between X and carboxyl group
  increases

7
19.7Ionization ofSubstituted Benzoic Acids
8
Hybridization Effect

• sp2-hybridized carbon is more electron-withdrawin
  g than sp3, and sp is more electron-withdrawing
  than sp2

9
Table 19.3 Ionization of Substituted Benzoic
Acids

• effect is small unless X is electronegative
  effect is largest for ortho substituent

pKa Substituent ortho meta para H 4.2 4.2 4.2 CH
3 3.9 4.3 4.4 F 3.3 3.9 4.1 Cl 2.9 3.8 4.0 CH3O 4.
1 4.1 4.5 NO2 2.2 3.5 3.4
10
19.8Dicarboxylic Acids
11
Dicarboxylic Acids
pKa
Oxalic acid
1.2
Malonic acid
2.8
Heptanedioic acid
4.3

• one carboxyl group acts as an electron-withdrawin
  g group toward the other effect decreases with
  increasing separation

12
19.9Carbonic Acid
13
Carbonic Acid

H2O
CO2
99.7
0.3
14
Carbonic Acid


H2O
CO2
H
15
Carbonic Acid


H2O
CO2
H
overall K for these two steps 4.3 x 10-7

• CO2 is major species present in a solution of
  "carbonic acid" in acidic media

16
Carbonic Acid
Ka 5.6 x 10-11
Second ionization constant

H
17
19.10Sources of Carboxylic Acids
18
Synthesis of Carboxylic Acids Review

• side-chain oxidation of alkylbenzenes (Section
  11.13)
• oxidation of primary alcohols (Section 15.10)
• oxidation of aldehydes (Section 17.15)

19
19.11Synthesis of Carboxylic Acids by the
Carboxylation of Grignard Reagents
20
Carboxylation of Grignard Reagents
Mg
CO2
RMgX
RX
diethylether
H3O

• converts an alkyl (or aryl) halide to a
  carboxylic acid having one more carbon atom than
  the starting halide

21
Carboxylation of Grignard Reagents
d
C
O


H3O
22
Example Alkyl Halide
1. Mg, diethyl ether
2. CO2 3. H3O
Cl
CO2H
(76-86)
23
Example Aryl Halide
1. Mg, diethyl ether
2. CO2 3. H3O
(82)
24
19.12Synthesis of Carboxylic Acidsby
thePreparation and Hydrolysis of Nitriles
25
Preparation and Hydrolysis of Nitriles
H3O
RX
heat
SN2
NH4

• converts an alkyl halide to a carboxylic acid
  having one more carbon atom than the starting
  halide
• limitation is that the halide must be reactive
  toward substitution by SN2 mechanism

26
Example
NaCN
DMSO
(92)
H2O
H2SO4
heat
(77)
27
Example Dicarboxylic Acid
BrCH2CH2CH2Br
NaCN
H2O
(77-86)
NCCH2CH2CH2CN
H2O, HCl
heat
(83-85)
28
via Cyanohydrin
1. NaCN
2. H
H2O
HCl, heat
(60 from 2-pentanone)